OBJECTIVE Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections, and the threat associated with CDI continues to grow in all patient populations. There is increasing evidence that CDI has a substantial impact on the morbidity and mortality in solid organ transplant (SOT) recipients. Furthermore, new diagnostic and treatment options and strategies for CDI have emerged over the last decade. The purpose of this review is to provide a general understanding of CDI and its evidence-based diagnosis and management strategies, with a focus on SOT recipients. RESULTS The incidence and severity of CDI have significantly increased since the year 2000. Studies have identified novel risk factors for CDI, and a new epidemic strain, the NAP1/BI/027, has emerged. Despite the development of newer testing methods and approaches, including nucleic acid amplification tests and testing algorithms, the optimal method for diagnosing CDI is an area of controversy. New agents for treating CDI are being developed, and the use of fecal microbiota transplantation to treat recurrent CDI in SOT recipients is also evolving. CONCLUSIONS CDI is a significant problem for SOT recipients. Further studies on diagnostic and therapeutic strategies with a focus on SOT recipients are needed to further improve patient outcomes.